The significance of mechanical stresses and strains in vascular cell biology and pathology are well recognized. A large number of problems in vascular physiology and patho- physiology depend on the stresses and strains in the cellular and extracellular matrix of the vessel wall. It is possible to measure the strains but not the stresses. The determination of the stresses requires a precise understanding of the mechanical properties of the tissue;i.e., we must know the constitutive equations for the different layers of the vessel wall. The objective of this proposal is to develop and experimentally validate a microstructural model of the adventitia of swine coronary arteries. The proposal involves Multi-Photon Microscopy (MPM) that enables the identification of elastin and collagen fibers of the coronary arterial adventitia under mechanical loading, and numerical methods that take advantage of modern computational capability to deal with the complex microstructural geometry and boundary conditions. The Specific Aims are: 1) To quantify the 3-D microstructure of collagen and elastin fibers in coronary arterial adventitia using MPM under simultaneous loading conditions;2) To develop a constitutive model based on the microstructural data in Aim 1 and to perform mechanical test with direct finite element (FE) simulations;and 3) To experimentally validate the constitutive model of Aim 2 with load-deformation relation under biaxial conditions for fibers and cells measured in normal and hypertensive adventitia. The major contributions of this proposal are three fold: First, the computational framework will provide a mathematical description of the structure-function relation of coronary arteries, and result in a new level of understanding of the mechanical response of the blood vessel. Second, the extensive experimental data of the microstructures in health and hypertension and their deformation will enrich the understanding of the mechanical environment of the fibers and fibroblasts. Third, the direct application of the proposed computational framework will clarify several important hypotheses in cardiovascular research, such as the microstructural basis of the increased stiffness of coronary arteries in hypertension. PUBLIC HEALTH RELEVANCE: Coronary artery disease remains a major cause of morbidity and mortality in the U.S. and around the world especially in patients with hypertension. There is no doubt that mechanical stresses and strains play an important role in vessel health and disease. The major contributions of this proposal is to provide a mathematical description of the structure-function relation of coronary arteries in health and hypertension, and result in a new level of understanding of the mechanical response of the blood vessel.